Classifying diseases according to symptoms is rapidly becoming a thing of the past. Targeted therapeutics have shown us that sets of symptoms can be caused by different pathogenic mechanisms. Now, Choy et al. demonstrate that asthma can be divided into three immunological clusters: TH2-high, TH17-high, and TH2/17-low. The TH2-high and TH17-high clusters were inversely correlated in patients. Moreover, neutralizing one signature promoted the other in a mouse model of asthma (also see the Focus by Shum). These data suggest that combination therapies targeting both pathways may better treat asthmatic individuals.